title: Local overexpression of interleukin-11 in the central nervous system limits demyelination and enhances remyelination.
abstract: Demyelination is one of the pathological hallmarks of multiple sclerosis (MS). To date, no therapy is available which directly potentiates endogenous remyelination. Interleukin-11 (IL-11), a member of the gp130 family of cytokines, is upregulated in MS lesions. Systemic IL-11 treatment was shown to ameliorate clinical symptoms in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. IL-11 modulates immune cells and protects oligodendrocytes in vitro. In this study, the cuprizone-induced demyelination mouse model was used to elucidate effects of IL-11 on de- and remyelination, independent of the immune response. Prophylactic-lentiviral- (LV-) mediated overexpression of IL-11 in mouse brain significantly limited acute demyelination, which was accompanied with the preservation of CC1(+) mature oligodendrocytes (OLs) and a decrease in microglial activation (Mac-2(+)). We further demonstrated that IL-11 directly reduces myelin phagocytosis in vitro. When IL-11 expressing LV was therapeutically applied in animals with extensive demyelination, a significant enhancement of remyelination was observed as demonstrated by Luxol Fast Blue staining and electron microscopy imaging. Our results indicate that IL-11 promotes maturation of NG2(+) OPCs into myelinating CC1(+) OLs and may thus explain the enhanced remyelination. Overall, we demonstrate that IL-11 is of therapeutic interest for MS and other demyelinating diseases by limiting demyelination and promoting remyelination.
authors.affiliation: Biomedical Research Institute, School of Life Sciences, Hasselt University and Transnational University Limburg, 3590 Diepenbeek, Belgium.
authors.forename: Anurag
authors.initials: A
authors.lastname: Maheshwari
authors.forename: Kris
authors.initials: K
authors.lastname: Janssens
authors.forename: Jeroen
authors.initials: J
authors.lastname: Bogie
authors.forename: Chris
authors.initials: C
authors.lastname: Van Den Haute
authors.forename: Tom
authors.initials: T
authors.lastname: Struys
authors.forename: Ivo
authors.initials: I
authors.lastname: Lambrichts
authors.forename: Veerle
authors.initials: V
authors.lastname: Baekelandt
authors.forename: Piet
authors.initials: P
authors.lastname: Stinissen
authors.forename: Jerome J A
authors.initials: JJ
authors.lastname: Hendriks
authors.forename: Helena
authors.initials: H
authors.lastname: Slaets
authors.forename: Niels
authors.initials: N
authors.lastname: Hellings
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002490:Central Nervous System / Q000378:metabolism* / Q000648:ultrastructure; D003471:Cuprizone / Q000494:pharmacology; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017370:Interleukin-11 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D009186:Myelin Sheath / Q000378:metabolism
chemical_list: D017370:Interleukin-11; D003471:Cuprizone